POS0361 DNA METHYLATION SIGNATURES CHARACTERIZE PSORIASIS AND PSORIATIC ARTHRITIS IN MONOZYGOTIC TWINS DISCORDANT FOR THE DISEASE

Background: Psoriatic disease is a chronic inflammatory disorder spanning from skin (psoriasis) to psoriatic arthritis (PsA). The genetic background insufficient explain onset as illustrated by not very informative Genome Wide Association Studies and monozygotic (MZ) twin studies recently performed. It strongly assumed that epigenetics may contribute susceptibility modulating gene expression. DNA methylation has been found involved in several autoimmune rheumatic diseases. Here we have analysed the profile of selected cohort MZ twins discordant for psoriasis/PsA. Objectives: To identify methylome associated with psoriasis PsA peripheral blood these conditions. Methods: Peripheral 7 couples was collected extracted genome-wide evaluation profile, Infinium MethylationEPIC BeadChip. Minfi packages Bioconductor were used analyse data obtained. Quality control exclusion criteria applied raw having final number 762.451 probes, which accounts 88% total. Results: approach first identified 2564 differentially methylated positions (DMPs; *p<0.005) 19 genes potentially affected (with at least two DMPs within 1 kb distance), including SMAD3 SMARCA4/BRG1 Interferon TGFβ pathways. Gene Ontology (GO) analysis DMP-associated showed significative enrichment (*p<0.005) transcription factor binding, corepressor coactivator activity, SMAD binding histone -lysine-N-methyltransferase activity. further validate results, 5’-methylcytosine immunoprecipitation (MedIP) followed Real Time PCR performed assess level promoters same twins. We significantly promoter (p<0.05). mRNA expression also assessed evaluate any inverse correlation level, on EPIC array (n=4) PsA/Ps patients (n=8) appropriate healthy controls (n=3). Reduced (p<0.05) demonstrated (n=4). Conversely, no changes SMAD3. Conclusion: report disease. believe observed SMARCA/BRG1 suggest an epigenetic imbalance chromatin remodelling factors inflammation pathways potential role PsA/psoriasis immunopathogenesis. Disclosure Interests: None declared